E coli bioconjugate vaccine(GlaxoSmithKline Plc)

Recurrent urinary tract infections (rUTIs) can be a difficult condition to treat, and the role of vaccines is unclear.

To systematically review the role of vaccines in the treatment of rUTIs, looking at efficacy, adverse events, and discontinuation from treatment.

We systematically reviewed the role of vaccines for rUTIs using the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) methodologies for all English-language articles from inception of databases to July 2018. Data were collected for different vaccine types, short- (≤6 mo) and long-term (>6 mo) efficacy, and adverse effects with risk of bias assessment of included studies.

After initial identification of 1680 articles, 36 abstracts were screened, 25 full-text articles were assessed, and 17 (including 3228 patients; 1970 in the vaccine group and 1258 in the comparison group) were included. There were three studies in Uromune, nine in OM-89/UroVaxom, four in Solco-Urovac, and one in ExPEC4 V groups. Uromune, UroVaxom, and Solco-Urovac reported on the short-term follow-up, and the overall efficacy for vaccination demonstrated a significant odds ratio (OR) of 0.17 (95% confidence interval [CI] 0.06-0.50). Uromune, UroVaxom, and ExPEC4 V reported on the long-term follow-up, and the overall efficacy for vaccination demonstrated a significant OR of 0.20 (95% CI 0.07-0.59). The reported side effects were mild and varied from 0% to 13% across studies, and treatment withdrawal or exclusion due to adverse events was reported in 11 patients.

Vaccines seem to have a short-term role in the prevention of recurrent urinary tract infections with tolerable side effects. However, due to lack of uniformity of definitions and long-term follow-up, more work needs to be done with inclusion of other high-risk patient groups.

In this study, we look at the role of vaccines for recurrent urinary tract infections. We found that they seem to have a short-term role in the prevention of recurrent urinary tract infections and might play an increasing role in the future.

ExPEC4V (JNJ-63871860) is a bioconjugate vaccine, containing O-antigens from Escherichia coli serotypes O1A, O2, O6A, and O25B, developed for the prevention of invasive extra-intestinal pathogenic E coli (ExPEC) disease. We aimed to assess safety, reactogenicity, and immunogenicity of ExPEC4V in healthy adults.

In this phase 2 randomised, double-blind placebo-controlled study, we recruited healthy adults (≥18 years with a body-mass index of 35 kg/m² or less) between Nov 16, 2015, and Aug 8, 2017, and randomly assigned them to receive a single dose of ExPEC4V (antigen O1A:O2:O6A:O25B content 4:4:4:4 μg [group 1]; 4:4:4:8 μg [group 2], 8:8:8:8 μg [group 3], 8:8:8:16 μg [group 4], or 16:16:16:16 μg [group 5]) or placebo. The primary objectives were evaluation of the safety, tolerability, and immunogenicity of ExPEC4V and determination of its dose-dependent immunogenicity 15 days after vaccination by ELISA in individuals who had received at least one vaccination dose. Antibody titres and safety evaluation were used to select two ExPEC4V doses for assessment up to day 360. This trial is registered at ClinicalTrials.gov, number NCT02546960.

Of 848 enrolled participants, 843 (99%) received the ExPEC4V vaccine (757) or placebo (86) and were included in the safety analysis. Of 757 participants vaccinated with ExPEC4V, 222 (29%) had a solicited local adverse event and 325 (43%) had any solicited systemic adverse event, compared with 11 (13%) and 30 (35%) of 86 participants in the control group. Symptoms were mild-to-moderate. The most frequently reported solicited local adverse event was pain or tenderness (205 [27·1%] of 757 in combined ExPEC4V groups) and the most frequently reported solicited systemic adverse event was fatigue (208 [27·6%] of 757). Only 13 (2%) of 843 had a grade 3 event. At day 15, 80% or more of all participants achieved a two times or greater increase in serotype-specific IgG antibodies (except O25B at the lowest dose, 103 [72%] of 144). At day 360, 66% (95% CI 56·47-74·33) of participants in group 2 and 71% (62·13-78·95) of participants in group 4 selected for long-term follow-up maintained a two times or greater increase in serotype-specific antibody compared with baseline.

EXPEC4V seemed well tolerated and elicited robust and functional antibody responses across all serotypes, doses, and age groups. For the two dosages evaluated (4:4:4:8 μg and 8:8:8:16 μg), the immune response persisted for 1 year.

Janssen Pharmaceuticals.